Detection of anti-M. leprae antibodies in children in leprosy-endemic areas: A systematic review

Abstract

Background Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients’ households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. Methods and findings A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. Conclusions Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.

Bacilloscopy and polymerase chain reaction of slit-skin smears and anti-phenolic glycolipid-I serology for Hansen’s disease diagnosis

“…Most of the published studies use IgM as a target molecule in serological assays because the seroprevalence of anti-PGL-I IgM is higher than the seroprevalence of IgA and IgG in endemic areas ( 27 ). IgM seropositive individuals are at increased risk of developing the disease ( 28 ); however, IgM seropositivity is not predictive of disease, as demonstrated with IgG APGL-I ( 29 , 30 ).…”

Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

“…In humans anti-PGL-I IgM has been reported on more often in leprosy research than anti-PGL-I IgG or -IgA (Pierneef et al, 2021). Monitoring the dynamic differences of anti-PGL-I IgM and IgG antibodies in sera from experimentally M. leprae infected armadillo provides insight into the formation and kinetics of these antibodies in humans at the early stage of infection.…”

“…Given the correlation between anti-PGL-I IgM levels and bacterial load (Tió-Coma et al, 2020;van Hooij et al, 2020), this humoral immunity biomarker is useful to detect M. leprae infection as well as diagnose MB patients (van Hooij et al, 2017(van Hooij et al, , 2019. Studies in humans on the kinetics of antibody production directly after M. leprae infection, including quantitative and qualitative differences between IgM and IgG, have been considerably constrained due to the facts that anti-PGL-I immunity cannot discriminate between past and present M. leprae infection (Pierneef et al, 2021), most humans do not develop disease after M. leprae infection and leprosy has a long incubation time (Scollard et al, 2006).…”

Advances in the Diagnosis of Leprosy

“…Though antibody levels provide some insight into the status of infection, but they are insufficient to distinguish between recent and past infections. However, finding the evidence of infection would suggest a recent transmission (17).…”